This proposal describes a B/START project that will use measures of neural synchrony in the electroencephalogram (EEG) to examine the functional integrity of neural circuitry in schizophrenia. Schizophrenia has been conceptualized as a failure of cognitive integration, and abnormalities in neural circuitry have been proposed as a basis for this disorder. We hypothesize that abnormalities in gamma-band EEG oscillations reflect impairments in the synchronization of neural circuits in schizophrenia, and are directly related to core cognitive impairments. (Please note that the PI is a newly independent investigator in schizophrenia research, having finished his postdoctoral training in this field 2 years ago, and thus is at an ideal stage in his career for a B/START grant.) Previously we reported two major abnormalities in the gamma-band oscillations elicited by visual Gestalt patterns in schizophrenics: 1) the stimulus-evoked oscillation (SEO) was absent, and 2) the response-locked oscillation (RLO) occurred in a lower frequency band for patients than controls. In schizophrenics, the RLO was positively correlated with visual hallucinations, thought disorder, and disorganization. We hypothesize that the absence of the SEO in schizophrenics is due to a lack of top-down attentional enhancement of synchrony at this stage of early visual processing, which would be consistent with the attentional deficits that characterize schizophrenia. Given that the RLO appears to be generated in visual cortex but is coupled to reaction time, and is related to core perceptual and cognitive dysfunctions in schizophrenia, we hypothesize that the RLO reflects a synchrony-based neural mechanism that is closely involved in the generation of conscious perceptions, and is sensitive to primary neural circuit abnormalities in schizophrenia. Thus, a better understanding of the functional significance of the SEO and RLO may lead to new insights into the neural substrates of cognitive dysfunction of schizophrenia. To test these hypotheses, we will examine neural synchrony in chronic schizophrenia patients and matched healthy controls while they perform visual perception tasks which presumably involve feature integration via neuronal synchronization. Our specific aims are to: 1) Test whether the absence of the SEO in schizophrenics is stimulus-independent, and 2) reflects a lack of attentional enhancement of synchrony. 3) Test that the RLO reflects a feature-binding mechanism involved in conscious object perception. 4) Confirm our previous findings of schizophrenic abnormalities and symptom correlations in the RLO. To treat and ultimately prevent neuropsychiatric disorders, we must understand how the mind and brain are interrelated. This project seeks to further this goal by studying how brainwave synchronization is related to perception and thinking in people who are healthy, and in people who have schizophrenia. [unreadable] [unreadable] [unreadable]